Chronic Disease Research Group
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Jon J. Snyder, PhD, MS, Director of Transplant Epidemiology
October 2, 2020
As I enter my 21st year as an epidemiologist in the field of solid organ transplantation, I am reminded of the healing and hope that organ donation and transplant brings to those facing a diagnosis of end-organ failure. In my inaugural contribution to the Chronic Disease Research Group (CDRG) blog, I hope to impart my respect and amazement for this field of medicine and attest to how it is meeting current challenges.
Before I address current challenges, let’s set the stage. Since the first kidney transplant in 1954 and passage of the National Organ Transplant Act (NOTA) in 1984, the field of solid organ transplantation has grown to include kidney, liver, heart, lung, pancreas, intestine, and vascularized composite allograft (VCA) transplantation. A change in federal regulations in 2014 added VCAs to the definition of solid organ transplant. VCAs include transplants of the face, scalp, upper limbs (arms), abdominal wall, and reproductive organs, including the penis and uterus.
In 2019, transplant surgeons performed a record number of 39,719 transplants, an impressive 9% increase over 2018. These life-saving or life-enhancing transplants were made possible by 7,387 living donors and 11,870 deceased donors, an 8% and 11% increase over 2018, respectively.1
However, the demand for transplants continues to exceed organ donations, despite these impressive gains. As of September 17, 2020, 108,945 patients were on the national waiting list. Patients who need a kidney or liver outnumber the transplants performed the previous year by far. Although the number of heart and lung transplants in 2019 surpassed that of waitlisted patients, 223 heart candidates died on the waitlist, and 301 were removed after becoming too sick to undergo transplant. Another 146 lung candidates died waiting, and 166 were removed due to declining health. Considering all organ waitlists, 5,164 candidates died waiting, and 5,752 were removed due to illness.
Transplant is made possible through generous gifts of living and deceased organ donors, and CDRG continues to support multiple efforts to increase organ donation. The Health Resources and Services Administration recently awarded CDRG the Scientific Registry of Transplant Recipients (SRTR) 5-year contract, marking CDRG’s 11th year operating SRTR. As part of SRTR work, CDRG also handles the Living Donor Collective, a registry that evaluates participants to become living liver or kidney donors. By expanding this registry on a national level, SRTR plans to study long-term outcomes of living donors to further understand and inform the field of living organ donation.
Procuring organs from deceased donors begins with donation authorization, either first-person (eg, organ donor designation via driver’s license) or with permission from next of kin. CDRG works with Donate Life America to produce the Registry Overview Report, which tracks nationwide progress for organ, eye, and tissue donor registration. The number of designated organ donors in state-based registries has nearly doubled over the time period shown, from 79,702,797 in 2008 to 158,556,330 in 2019. In addition, the National Donate Life Registry contained more than 5 million registrations by the end of 2019.
Trend in State-Based Donor Designations
Under SRTR, CDRG also supports the nation’s transplant system by producing the OPTN/SRTR Annual Data Report. Published each year in the American Journal of Transplantation (AJT), CDRG produces semiannual reports on the performance of transplant programs and organ procurement organizations (OPOs) to improve organ allocation policy development. The Organ Procurement and Transplantation Network (OPTN) is developing organ allocation policies according to a continuous distribution framework, as illustrated by an SRTR publication in AJT.
While we celebrate successes in the field, 2020 has been a challenging year. COVID-19 caused rapid changes at donor hospitals, OPOs, and transplant programs. SRTR recently launched a web application detailing the pandemic’s impact on the national transplant system. The monthly number of kidney transplants declined 45% in the month after the national emergency declaration (see figure below).
A closer look at kidney transplant numbers reveals that living donor kidney transplants (red line) declined 86% that month, dropping to just 73 living donor transplants from March 13 to April 12, in contrast with 526 a month before the emergency.
However, a turnaround occurred in the third month after the declaration (shown in the second month of both figures). Kidney transplants from brain-dead donors (DBDs) reverted to numbers seen before the pandemic, while kidney transplants from living donors and donations following circulatory death (DCDs) remained slightly below pre–COVID-19 numbers. (Note that the most recent analyses above may be incomplete because data are updated monthly.)
The number of donors decreased about 25% in the first two months of the pandemic in the United States and returned to pre-emergency levels the next month. I believe this demonstrates the laudable dedication of personnel in the national transplant system to giving the gift of life to those in need. SRTR continues to evaluate the effects of COVID-19 on the system and updates the application monthly.
I hope my appreciation for the organ donation and transplantation field inspires action. The need for organ donation continues to be great, so please consider designating yourself as an organ, eye, and tissue donor through your state’s registry or at www.registerme.org. Our team extends our best to those working on the frontlines of the transplant system during COVID-19. Your work is vital to so many in need.
1. Organ Procurement and Transplantation Network. https://optn.transplant.hrsa.gov/data/view-data reports/national-data# (accessed September 18, 2020.)
Eric D. Weinhandl, PhD, MS, Senior Epidemiologist
September 1, 2020
Well, not quite tomorrow. Maybe a few years from now.
In the United States and around the world, peritoneal dialysis (PD) is an incident therapy. In other words, most PD prescriptions are written for patients who are initiating dialysis for the treatment of end-stage kidney disease (ESKD). There are both psychosocial and clinical reasons for this. For patients who are transitioning from a life with chronic kidney disease to a life with chronic dialysis, the possibility of continuing to live and dialyze at home can be very attractive. On the other hand, nephrologists may be interested in preserving both residual kidney function — which is strongly associated with improved survival in dialysis patients — and the arm vasculature that is needed for an arteriovenous fistula, should hemodialysis (HD) be prescribed in the future.
In fact, for many patients who select PD, HD is a part of the future. However, even if nephrologists and nurses know this, it can be difficult to counsel patients and families about the future. Is PD a therapy for a lifetime? Is PD a mere transitional therapy to a life with in-center HD? Is PD somewhere in the middle of those extremes?
New data published in Kidney Medicine provides some answers, as well as historical perspective on PD in the United States (US). In an analysis from the United States Renal Data System (USRDS), Sukul and colleagues evaluated rates of kidney transplant, transition to in-center HD (sometimes labeled as “technique failure”), and death in US patients who initiated PD within the first six months after the diagnosis of ESKD. Interestingly, the authors evaluated patients who were diagnosed with ESKD between 1996 and 2014, thus creating an opportunity to examine the evolution of event rates across calendar years.
Patients were followed from the first day of PD, which could have occurred as early as the very first day of chronic dialysis or as late as six months after an ESKD diagnosis, until the earliest of kidney transplant, transition to in-center HD, or death, with censoring for kidney function recovery and discontinuation of dialysis (an outcome that is a little murky, but occurs much less often than death due to withdrawal from dialysis). Follow-up was strictly limited to three years after the first day of PD — a tremendously important point of context. Patients were grouped into years of ESKD incidence: 1996-1999, 2000-2003, 2004-2007, 2008-2011, and 2012-2014. The authors compared the rates of each outcome among the groups, with adjustment for factors that are on form CMS-2728 (ie, the Medical Evidence Report) and the annual census of the PD program.
Let’s discuss some of the most interesting results:
The big picture is that today’s PD patients can be counseled with relative confidence that life with PD is not a mere transitional state. If one adds the rates of kidney transplant, transfer to in-center HD, and death among patients with newly diagnosed ESKD in 2014, the sum is nearly 40 events per 100 patient-years. Think about the reciprocal of that quantity: 2.5 patient-years per event. In other words, a patient who is newly prescribed PD can expect to spend about 30 months with the modality before a good (transplant), neutral (transfer to in-center HD), or bad (death) outcome occurs. Furthermore, if neither transplantation nor death occurs, then the likelihood of remaining on PD after three years is a little higher than the chance of seeing heads upon the flip of a fair coin. I would contend that an appropriate conclusion from all of this is that three to five years with PD is a very realistic outcome.
Of course, another conclusion is that hemodialysis is a possible destination along the journey of ESKD. For many patients, PD will not be a lifetime therapy. We must communicate honestly to patients and their families that modalities can and do change. From that perspective, it is important for researchers and policymakers to thoughtfully consider how to incorporate the transition from PD to in-center HD in quality measures. Some of these transitions are preventable and many are very disruptive, with extensive hospitalization due to intercurrent illness. However, transitions may also be what patients prefer. If we are truly committed to patient autonomy in selecting kidney replacement therapies, then we must respect that the goal rate of transition to in-center HD is not necessarily equal to zero events per 100 patient-years. How to operationalize this thought is a great challenge for a future that widely encourages home dialysis.
One of the unintended consequences that likely accompanies home dialysis evaluation is increasing PD selectivity — or home HD, for that matter. Plainly stated, selectivity for home dialysis is a dangerous enticement. One could argue that Sukul and colleagues have shown selecting healthier patients for PD is the most expedient way to lower death rates on PD. In the era of Advancing American Kidney Health (AAKH), we must resist this temptation, however difficult that may be for dialysis facilities that are so often graded according to relative clinical outcomes. If we cast wider nets for home dialysis, including for patients with substantial comorbidity and frailty, then we should expect that death rates on PD will increase and rates of kidney transplantation will decrease. For that matter, transition rates from PD to in-center HD may increase. Even the reported association of larger PD program sizes with lower transition rates to in-center HD is sensitive to selectivity. There is likely a technical component to this association, insofar as “practice makes perfect.” However, the largest PD programs — those that try to train all patients with newly diagnosed ESKD to perform home dialysis — are likely to exhibit relatively poor outcomes, because some of the underlying medical and social challenges that dialysis patients face are effectively transferred from the pool of in-center HD patients to the pool of PD patients.
We are making progress with PD, and we need to keep making progress, because longevity of home dialysis mathematically influences overall utilization of home dialysis. Nevertheless, I hope that we do not grow too beholden to hard measures like transition rates. The goal is to deliver high-quality, patient-centered dialysis — not necessarily one modality per lifetime.
Eric D. Weinhandl, PhD, MS, Senior Epidemiologist
July 27, 2020
Every summer, the Centers for Medicare and Medicaid Services (CMS) releases a proposed rule regarding the End-Stage Renal Disease (ESRD) Prospective Payment System (PPS) and Quality Incentive Program (QIP). Essentially, the proposed rule lists potential updates to Medicare policy—including reimbursement—pertaining to outpatient dialysis facilities, effective at the beginning of the next calendar year.
The most important news is that, like every year, anyone can participate in rulemaking.
Are you a nephrologist? A nurse? A social worker or dietitian? Are you a researcher? Are you a patient undergoing dialysis? Do you have a stake in the future of dialysis? If the answer to any of these questions is “yes,” you should consider offering comments to CMS.
The proposed rule is published in the Federal Register. On the linked page there is a large green button labeled “Submit a Formal Comment.” Click that button and write your comments. The submission deadline is September 4, 2020. I wrote a few comment letters in the past, so I have a few pieces of advice:
This year’s proposed rule tallies 77 pages in the Federal Register, a government publication that usually includes three columns per page. My goal is to highlight several important items in the proposed rule that should merit attention from anyone who cares about dialysis. I do not aim to share personal remarks about these items. (I’ll save my opinions for my comment letter.) I do hope that by distilling 77 pages into a set of questions, you might be able to more efficiently craft a comment letter that strikes the heart of the matter. So, without further delay:
CMS proposes to add calcimimetics to the bundled payment for outpatient dialysis in 2021. In 2018-2020, calcimimetics—oral cinacalcet and intravenous etelcalcetide—were separately reimbursable via the Transitional Drug Add-on Payment Adjustment (TDAPA). TDAPA is actually intended to apply for two years, not three, so the inclusion of calcimimetics in the bundle is not a surprise.
The core question is this: what is an appropriate amount of money for CMS to pay for calcimimetics? It is a difficult question to answer because of two important developments during the TDAPA application: the arrival of generic cinacalcet and the introduction of oral etelcalcetide. The derivation of an appropriate amount is further complicated by CMS' goal to add a single amount per hemodialysis session, even though only 30% of hemodialysis patients use calcimimetics.
Let’s start with CMS’ math. The agency queried Medicare claims from outpatient dialysis facilities in 2018 and 2019. In so doing, CMS found that dialysis facilities dispensed or administered the following amounts to patients with Medicare Part B coverage:
CMS proposes to multiply each quantity by the respective average sales price (ASP) of each agent in the most recent quarter. In the Federal Register, that quarter is the second quarter of 2020. In the forthcoming final rule, CMS will likely use ASPs in the third or fourth quarter of 2020. Does this matter? Yes. Look at the trajectory of ASPs for cinacalcet and etelcalcetide since the first quarter of 2018:
In the proposed rule, CMS used ASPs of $0.231 per mg for cinacalcet and $22.00 per mg for etelcalcetide. Thus, CMS derived total calcimimetic expenditures in 2018-2019 that were equal to:
1,824,370,597 × $0.231 + 30,671,241 × $22.00
CMS also identified 90,014,098 hemodialysis-equivalent sessions, whereby one day of peritoneal dialysis is equal to three-sevenths of a hemodialysis session. Thus, the agency derived a bundled payment rate for calcimimetics equal to:
$1,096,200,947 / 90,014,098
The outlier policy shaved 1% off this amount, leading to the proposal of $12.06.
That is the algorithm. These are the questions to consider:
Last year, CMS created the transitional add-on payment adjustment for new and innovative equipment and supplies (TPNIES). Essentially, TPNIES intends to add an amount to the bundled payment for outpatient dialysis to incentivize “new” (FDA marketing authorization after January 1, 2020) and “innovative” (more on that in a moment) dialysis-related supplies that are not capital-related assets. If approved under TPNIES, CMS would authorize for two years a per-treatment payment equal to 65% of the supply price determined by the local Medicare Administrative Contractor (MAC).
What is innovative? CMS defined it last year as a supply satisfying the “substantial clinical improvement” (SCI) criteria. Briefly, SCI implies that a supply “substantially improves, relative to renal dialysis services previously available, the diagnosis or treatment of Medicare beneficiaries.” There are several ways to prove SCI:
CMS indicated that evidence might be derived from randomized and non-randomized studies. The first applicant for TPNIES is Baxter’s series of Theranova 400 and 500 dialyzers; the series numbers indicate differences in surface area. These are medium cut off dialyzers.
CMS evaluated evidence and concluded that there is “insufficient evidence at this time to demonstrate a clear clinical benefit for Medicare dialysis patients.” The agency solicits your opinion about whether Theranova dialyzers satisfy the SCI criteria.
The second applicant for TNPIES is Outset Medical’s Tablo cartridge for the Tablo Hemodialysis system. The Tablo Hemodialysis system is a new hemodialysis platform, which can be used in the facility setting and was recently cleared by the FDA for use in the home setting. The cartridge is a single-use, disposable arterial and venous bloodline set. More information can be found in FDA documents and on the KidneyViews blog.
CMS evaluated evidence and concluded the following: “The cartridge is a promising concept to encourage home hemodialysis, but again, the evaluation of this technology is complicated by the need to also peripherally assess the [Tablo Hemodialysis] system… Within the larger policy context of FDA approval and the fact that TPNIES does not currently cover capital-related assets, the CMS TPNIES Work Group believes there are some irregularities and misalignments in the current application, and is concerned that the standalone cartridge cannot be evaluated for meeting the criteria for SCI.” The agency solicits your opinion about whether the Tablo cartridge alone satisfies the SCI criteria.
This is an interesting proposal. As I mentioned earlier, the TPNIES program currently in effect excludes capital-related assets. The definition of such an asset is actually a part of this year’s proposal; if finalized, the definition would be “an asset that an ESRD facility has an economic interest in through ownership (regardless of the manner in which it was acquired) and is subject to depreciation.” CMS notes that equipment obtained by the ESRD facility through operating leases are not considered capital-related assets.
What is new this year is a proposed expansion of TPNIES into capital-related assets that are home dialysis machines—either for home hemodialysis or peritoneal dialysis—when used in the home for a single patient. CMS notes that this proposal is motivated by the broad goals of the Executive Order on Advancing American Kidney Health. That order imagines that 80% of incident ESKD patients in 2025 would receive a kidney transplant or dialyze in the home.
The broad outlines of the proposal are the following:
Let’s make that last point concrete. Imagine that a new hemodialysis machine has a price of $20,000. Of course, 65% of $20,000 is $13,000. Five-year straight-line depreciation results in an annual cost of $13,000 divided by five, or $2,600. If the machine is used four times per week, then there are 208 treatments per year, so the TNPIES payment is $2,600 divided by 208, or $12.50 per treatment.
This proposal may be an effective way to motivate increased utilization of home dialysis modalities. CMS seeks comments about all aspects of its proposal, including SCI criteria and payment methodology. I encourage commenters to consider how SCI criteria can be applied to home dialysis machines, especially insofar as machines and prescriptions together influence the outcome of dialysis. Ask yourself this: when can a machine, by its very nature, satisfy SCI criteria? I also encourage commenters to consider whether payment methodology details are appropriate, especially in the case of home hemodialysis machines that might be used between two and six times per week.
Many in the kidney community, including myself, have advocated for greater utilization of home dialysis. Can this proposal—or a modification of it—be a meaningful part of incentivizing greater utilization? That is the question before all of us.
CMS proposes once again to set payment for hemodialysis sessions in acute kidney injury (AKI) patients equal to payment for hemodialysis sessions in ESKD patients. Thus, reimbursement would increase to $255.59 in 2021, but would presumably be subject to further revision in the final rule, owing to specific ASPs for calcimimetics. Although CMS did not ask for comments about this approach, I would encourage commenters to discuss whether continued alignment between dialysis for AKI and dialysis for ESKD is appropriate.
CMS proposed several other items, including changes to outlier payments, low-volume payment adjustments, wage indices, and the specifications of several QIP measures, but this blog entry is already long enough. I think that calcimimetics and the evolving TPNIES program are the stars of this year’s proposed rule, so focusing comments in those domains is a good idea, especially if your time is limited during July and August. Good luck writing!
Eric Weinhandl, PhD, MS, Senior Epidemiologist
July 1, 2020
This entry is the first in a new blog published by the Chronic Disease Research Group (CDRG) in Minneapolis, Minnesota. The goal of this blog is to provide visibility into medical research and health care policy news that intersect with the diverse areas of expertise among CDRG investigators.
As the public may know, CDRG has long been involved in nephrology research, including operating the United States Renal Data System (USRDS) Coordinating Center. I myself returned to CDRG after spending the past half-decade at NxStage Medical and Fresenius Medical Care North America. I am always interested in the latest from the domain of observational (ie, non-randomized) research about chronic dialysis. I would like to discuss a fantastic study of dialysis population data from Europe.1
The title immediately reveals a twist on an old topic. About 10 years ago, Robert Foley and colleagues published a study in the New England Journal of Medicine about the long interdialytic gap, a roughly 72-hour interval between consecutive hemodialysis sessions on Friday and Monday or Saturday and Tuesday.2 In that study, which included over 32,000 patients, the mortality rate on the day after the long interval was 23% higher than on other days, and the cardiovascular hospitalization rate was 124% higher. These findings were later corroborated by patterns of cardiovascular death in the Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA).3, 4
One might hypothesize that if a 72-hour gap between consecutive hemodialysis sessions is deleterious for volume control and electrolyte (eg, potassium) balance, then an even longer gap—a product of missing the first hemodialysis treatment of the week—is even worse. That is the question that the new study by Fotheringham and colleagues aims to answer. The irony of the question is that the study at hand reflects the experience of patients in Europe, whereas the problem of missed hemodialysis sessions is prominent in the United States. In a recent study from DOPPS investigators, the prevalence of at least one missed hemodialysis session per month was 7.9% in the United States—far above the corresponding prevalence estimates of 0.6% in a set of five large European countries and Japan.5
The authors of the study used data from the Analyzing Data, Recognizing Excellence, and Optimizing Outcomes (ARO) cohort study of patients who initiated hemodialysis in one of 312 Fresenius Medical Care dialysis facilities across 15 countries in Europe. Patients initiated dialysis between 2007 and 2009—admittedly, quite a while ago—and were followed through 2014. The study was limited to in-facility hemodialysis patients with thrice-weekly schedules that were identified as Monday-Wednesday-Friday (MWF) or Tuesday-Thursday-Saturday (TTS).
The study included almost 9,400 patients and approximately 3.8 million scheduled treatment days. Despite the volume of data, the design of the study was relatively simple. The design is summarized by Figure 1 in the article:
The middle of the above figure is the “anchor.” In other words, each observation in the study was a scheduled hemodialysis session. That session may or may not have been attended. Only scheduled sessions that were preceded by perfect adherence (and the absence of hospitalization) during the preceding 7-day interval were retained for analysis. Missed treatments on a scheduled day did not reflect hospitalization or death on that day, as such instances were excluded. After each scheduled session, patients were followed for 48 to 72 hours to assess the incidence of death and hospitalization. In other words, the authors took the phenotype of a dialysis patient with stability in the outpatient setting, tested whether a “surprising” missed treatment was associated with poor outcomes, and assessed whether the day of the dialytic week influenced the strength of that association.
It turns out that nothing is new under the sun, with respect to predictors of missed treatments. In particular, the mean age of patients who missed treatments during the first four months of follow-up was roughly three years younger than the mean age of patients with perfect adherence. Predictably, comorbidity was associated with higher likelihood of missed treatments, which may just be a manifestation of older age.
So, what do the models of death and hospitalization tell us? Well, the authors present a lot of figures, but let’s stick with two: Figure 3B, which shows adjusted hazard ratios of death, by day of week and attendance status; and Figure 4B, which shows adjusted hazard ratios of hospitalization, by day of week and attendance status. Hazard ratios of death are shown below:
Notice that the vertical axis is a logarithmic scale. In other words, patients who missed treatments had 10 to 50 times the mortality risk of patients with perfect adherence. Patients who missed the first hemodialysis session of the week were at the highest risk, whereas one might say that patients who missed the last hemodialysis session of the week were at a “less profoundly” elevated risk. It should be noted that in patients with perfect adherence, risk of death was highest after the first day of the hemodialysis week. That’s an interesting observation, as these patients attended not only all three sessions during the previous 7-day interval, but also the session on the scheduled day at hand. One cannot help but wonder if aggressive ultrafiltration is the culprit, although that’s a question for another study.
Hazard ratios of hospitalization are shown below:
The pattern is qualitatively similar. Patients who missed the first hemodialysis session of the week were at the very highest risk of hospitalization, whereas patients who missed the last hemodialysis session of the week were at a “less profoundly” elevated risk.
This is an observational study, and like all such studies, it is possible that confounding factors are chiefly responsible for data patterns. The authors suggest that “acute illness which both prevents attendance for scheduled dialysis and leads to hospital admission or death” could be a culprit. It’s important to acknowledge this possibility.
However, the reality of the accumulated literature is this:
The proximal challenge facing dialysis in the United States is addressing missed treatments, especially on the first day of the dialysis week. Providing resources to ensure transportation to and from the dialysis facility, and providing patients with treatment reminders via text message are two of many options that should be embraced.8 Interventions that lower the frequency of missed treatments are likely to confer positive effects on the risk of fluid- and electrolyte-mediated cardiac events. Considering the strength of associations in this study, one might argue that missed treatments on the first day of the dialysis week ought to be “never events” that are assessed in quality measurement systems.
The broader question is what to do about all the interdialytic gaps. Wider utilization of peritoneal dialysis (PD) in incident end stage kidney disease patients would be an excellent start, as the continuous nature of PD eliminates the concept of the interdialytic gap. Frequent home hemodialysis is another solution, albeit far from a universal one. What can be done for patients who cannot or will not dialyze at home? As a population-wide intervention, frequent in-facility hemodialysis tends to exhibit low cost-effectiveness, as demonstrated in international literature.9 However, a one-size-fits-all solution is the problem. As Hostetter recently wrote, “[D]ialysis care must be one of the least ‘personalized’ sectors of current health care.” 10 We need to continue designing systems that facilitate adaptations of in-facility hemodialysis for risk-stratified groups, such as:
The first category of patients can continue to dialyze three times per week, but the second category of patients will require every-other-day dialysis, thereby creating demand for Sunday shifts in dialysis facilities or community houses for “drop-in” self-care hemodialysis. The last category of patients is the most complex to manage, as they will require four to six treatments per week. Can all these patients be treated at home? This is unlikely. Could these patients mix in-facility and home treatments? With appropriate financial resources, it is possible. What seems clear to me is that business as usual, with almost universal application of thrice-weekly hemodialysis, will continue to produce sawtooth patterns in daily rates of death and hospitalization.